Causes of 5-Year Chronic Dyspepsia with Normal LFTs

1. Functional Dyspepsia (Most Common - 70-80% of cases)

• Definition (Rome IV): Bothersome postprandial fullness, early satiety, or epigastric pain/burning for ≥6 months with no identifiable organic cause
• Two subtypes:
  • Postprandial Distress Syndrome (PDS) - meal-induced fullness, early satiety (prevalence 6.1%)
  • Epigastric Pain Syndrome (EPS) - epigastric pain or burning, may be meal-unrelated (prevalence 2.4%)
• Mechanisms: Impaired gastric accommodation, visceral hypersensitivity, delayed gastric emptying, CNS-gut axis dysregulation, hypothalamic-pituitary-adrenal axis dysfunction, altered bile salt composition
• Associated conditions: IBS, fibromyalgia, chronic fatigue, anxiety, depression

2. Gastroesophageal Reflux Disease (GERD)

• Heartburn/regurgitation affects 18-28% of the population
• 5+ years of GERD symptoms warrant endoscopy to screen for Barrett's esophagus (6x increased risk vs <1 year of symptoms)
• Can present as pure dyspepsia (epigastric burning/fullness) without classic heartburn
• Normal LFTs expected

3. Peptic Ulcer Disease (PUD)

• Gastric or duodenal ulcers cause a minority of dyspepsia cases
• H. pylori infection - the most common cause of peptic ulcers; also plays a minor role in functional dyspepsia directly
• NSAID use - second most common cause; consider if patient uses analgesics regularly
• Rare causes: Crohn's disease, Zollinger-Ellison syndrome (gastrin-secreting tumor)

4. Gastroparesis

• Delayed gastric emptying causes postprandial fullness, nausea, bloating, early satiety
• 20% of gastroparesis patients report pain as the predominant symptom (mimicking dyspepsia without obvious nausea/vomiting)
• Causes: diabetic autonomic neuropathy, post-viral, post-surgical, idiopathic
• Normal LFTs expected

5. Biliary Causes (Normal LFTs possible)

• Gallstone disease / biliary colic - LFTs can be entirely normal between episodes; usually presents as discrete RUQ/epigastric episodes rather than constant burning, but can mimic dyspepsia
• Biliary dyskinesia (gallbladder dysmotility) - HIDA scan with CCK shows low ejection fraction; LFTs normal
• Note: chronic, dull epigastric discomfort is less typical of biliary colic

6. Dietary Intolerances

• Lactose intolerance - gas, bloating, discomfort (more common in Black and Asian populations)
• Fructose/sorbitol intolerance - similar symptoms
• Non-celiac gluten sensitivity - bloating, abdominal discomfort, dyspeptic symptoms without small bowel damage; LFTs normal

7. Celiac Disease

• Can present with bloating, epigastric discomfort, and dyspeptic symptoms
• LFTs can be mildly elevated (transaminases) or normal
• Diagnosed by anti-tTG IgA + duodenal biopsy; check serology if not already done

8. Small Intestinal Bacterial Overgrowth (SIBO)

• Causes dyspepsia, distention, bowel dysfunction, malabsorption
• Diagnosed by glucose/lactulose hydrogen breath test
• Normal LFTs expected

9. Pancreatic Disease

• Chronic pancreatitis - episodic to constant epigastric pain, often post-prandial; LFTs usually normal unless biliary compression
• Pancreatic malignancy - in a 5-year history this is less likely to be the full duration, but consider in older patients; early disease can have normal LFTs
• Check serum amylase/lipase, CT abdomen if suspected

10. Drug/Substance-Induced

• NSAIDs/analgesics - direct gastric mucosal irritation
• Theophylline, nitrates, calcium channel blockers, progesterone - promote gastroesophageal reflux
• Alcohol, tobacco, caffeine - lower LES tone, promote reflux
• Review medication list carefully

11. Metabolic / Endocrine

• Thyroid disease (hypo- or hyperthyroidism) - can cause dyspeptic symptoms; check TSH
• Hyperparathyroidism - hypercalcemia causes nausea, abdominal pain, dyspepsia; check serum calcium
• Normal LFTs expected

12. Less Common Causes to Consider

Practical Approach to Workup

1. H. pylori testing (urea breath test or stool antigen) - first step if not tested
2. Upper endoscopy (EGD) - indicated given >5 years of dyspepsia, especially if age >50 or any alarm features (weight loss, dysphagia, bleeding, anemia)
3. Abdominal ultrasound - rule out gallstones, biliary pathology
4. Serology: TSH, serum calcium, anti-tTG IgA (celiac), fasting glucose
5. Gastric emptying scan if gastroparesis suspected
6. HIDA scan with CCK if biliary dyskinesia suspected

• Unexplained weight loss
• Recurrent vomiting
• Dysphagia / odynophagia
• Occult/overt GI bleeding
• Iron deficiency anaemia
• Jaundice (absent here)
• Palpable mass / lymphadenopathy
• Family history of GI malignancy

Recent Clinical Guidelines on Functional Dyspepsia (2024-2026)

Key Documents Identified

Definition & Diagnosis (Rome IV - Current Standard)

• Postprandial fullness (bothersome, at least 3 days/week)
• Early satiation (at least 3 days/week)
• Epigastric pain (at least 1 day/week)
• Epigastric burning (at least 1 day/week)

• Postprandial Distress Syndrome (PDS) - meal-triggered fullness/early satiety
• Epigastric Pain Syndrome (EPS) - epigastric pain/burning, meal-independent or related

• FD is a diagnosis of exclusion (Italian, Belgian consensus)
• Patients should receive a positive diagnosis with explanation and reassurance, not just "exclusion of disease" (Belgian consensus)
• Co-existence with IBS and other disorders of gut-brain interaction (DGBI) is common and expected
• Bloating and weight loss can also occur in FD (Belgian consensus, 2025)

When to Perform EGD (Upper Endoscopy)

• EGD with biopsies is required in patients aged ≥45 years, OR with alarm symptoms, OR who are refractory to treatment
• EGD is NOT routine in young, low-risk patients without alarm features

• Unintended weight loss
• Dysphagia / odynophagia
• Recurrent vomiting
• GI bleeding / iron-deficiency anemia
• Family history of upper GI malignancy
• Palpable mass or lymphadenopathy

H. pylori Testing

• All FD patients should be tested for H. pylori (invasive or non-invasive - urea breath test or stool antigen preferred)
• All H. pylori-positive patients should receive eradication therapy - "test and treat" remains first-line strategy
• H. pylori eradication provides modest but real symptom benefit in a subset of FD patients (NNT ~14)

Pharmacological Treatment (2025 Updates)

First-Line:

Second-Line / Subtype-Specific:

Newer / Emerging Therapies (2024-2025 updates):

• Potassium-competitive acid blockers (P-CABs): Emerging data, especially in Asia; Asian consensus acknowledges limited scope of current studies
• Probiotics: Microbiome-modulation is a research target; promising but not yet guideline-standard (Olson et al., 2024)
• Low-FODMAP diet: Some benefit; being studied in large trials (Olson et al., 2024)
• Gut-directed hypnotherapy / virtual reality gut-brain therapy: Novel delivery methods showing promising results (Olson et al., 2024)
• Antibiotics (rifaximin): Exploratory target given SIBO-FD overlap; not currently recommended routinely (Belgian consensus recommends against antibiotics)

Non-Pharmacological Management

• Explanation and reassurance are the cornerstone of management (Belgian consensus)
• Healthy lifestyle advice is appropriate and recommended
• Exclusion / restrictive diets are discouraged (Italian and Belgian both advise against)
• Cognitive behavioural therapy (CBT) is recommended for patients who fail medical therapy (Italian guideline)
• Osteopathy and most complementary/alternative medicine: insufficient evidence to recommend (Italian, Belgian)

Pathophysiology Updates (2024-2025)

• Intestinal microbiome alterations and impaired intestinal membrane integrity (leaky gut) are now recognized as potentially important (Olson et al., 2024)
• CNS-gut axis dysregulation (functional MRI evidence of altered brain activation)
• Altered bile salt composition
• Duodenal low-grade inflammation and eosinophilia
• Post-infectious FD (post-COVID-19 gut dysfunction is an emerging area)

Summary Table: 2025 Guideline Recommendations at a Glance

What the flowchart covers (top to bottom):

1. Entry - Patient with upper abdominal symptoms
2. Duration gate - Symptoms ≥6 months? (Rome IV threshold)
3. Alarm features screen - With a full list of red-flag features in a side box; if present → urgent EGD pathway
4. Routine bloods + H. pylori testing - Mandatory in ALL patients
5. H. pylori eradication - Test-and-treat branch before FD confirmation
6. FD diagnosis + subtype identification - PDS vs EPS
7. First-line treatment - Standard-dose PPI 4-8 weeks (higher dose not beneficial)
8. Response assessment - Adequate response → PRN/step-down; no response → second-line
9. Second-line by subtype - PDS: prokinetics | EPS: TCAs / mirtazapine
10. Re-assessment at 6-8 weeks - Response vs refractory branch
11. Refractory FD pathway - Three parallel tracks: re-evaluate diagnosis, CBT/psychological therapy, pharmacological review + specialist referral
12. Ongoing management - Shared-care, reassurance, avoid restrictive diets and opioids
13. Key principles, abbreviations, and full source citations at the bottom

Low-FODMAP Diet

What are FODMAPs?

1. Poor absorption in the small intestine (small bowel permeability is variable and often incomplete)
2. Rapid fermentation by colonic bacteria, producing gas (H₂, CO₂, CH₄)

The Five FODMAP Categories

Mechanism of Action

High-FODMAP food ingested
        ↓
Poor absorption in small intestine (osmotic load)
        ↓
Water drawn into gut lumen → loose stool / urgency
        ↓
FODMAPs reach colon → rapid bacterial fermentation
        ↓
Gas production (H₂, CO₂, CH₄)
        ↓
Luminal distension → activates mechanoreceptors
        ↓
In visceral hypersensitivity (IBS/FD): exaggerated pain, bloating, urgency

The Three-Phase Protocol (Monash University)

Phase 1 - Strict Elimination (2-6 weeks)

• Eliminate ALL high-FODMAP foods
• Aim: establish a symptom-free or near-symptom-free baseline
• Must be supervised by a dietitian - nutritional adequacy is a concern
• ~75% of IBS patients achieve meaningful symptom reduction

Phase 2 - Systematic Reintroduction (6-8 weeks)

• Reintroduce one FODMAP subgroup at a time, every 3 days
• Identify personal triggers - most patients tolerate some FODMAPs (fewer than half of food challenges provoke symptoms)
• The gut is highly individual: triggers vary person to person

Phase 3 - Personalised Long-Term Diet

• Only the personally identified triggers remain restricted
• Most foods tolerated during Phase 2 are reintroduced
• Avoids unnecessary long-term nutritional restriction

Important: The diet should never remain in full elimination phase long-term. FODMAPs (prebiotics) feed beneficial gut bacteria and a permanently restricted diet reduces microbiome diversity.

Food Lists

LOW-FODMAP (Generally Safe) Foods

HIGH-FODMAP (Avoid in Phase 1) Foods

Clinical Evidence (2024-2025 Updates)

Best evidence: IBS

• 28 RCTs, 2,338 patients, 11 dietary interventions compared
• Low-FODMAP diet ranked 4th for global IBS symptoms (RR of non-improvement 0.51, 95% CI 0.37-0.70) vs habitual diet
• Best for abdominal bloating among interventions studied in multiple trials (RR 0.55)
• Notably, a starch/sucrose-reduced diet ranked above low-FODMAP for overall symptoms - suggesting low-FODMAP is effective but not uniquely superior
• Low-FODMAP was superior to standard BDA/NICE dietary advice for bowel habit

• Low-FODMAP + traditional dietary advice vs low-carbohydrate diet vs optimised pharmacological treatment (n=294)
• 76% response rate in low-FODMAP group vs 71% low-carb vs 58% pharmacotherapy at 4 weeks
• Dietary interventions were significantly superior to drug treatment (p=0.023)
• At 6-month follow-up, symptom benefits were maintained in both dietary groups

• Blinded reintroduction phase: systematic FODMAP reintroduction is safe and allows most foods to be returned to diet without symptom relapse

Evidence in Functional Dyspepsia

Nutritional Concerns

• Fibre intake drops (prebiotic loss - reduced Bifidobacterium and Lactobacillus)
• Calcium risk if dairy eliminated without lactose-free alternatives
• Microbiome diversity decreases with prolonged restriction
• Complex to implement - dietitian supervision is strongly recommended
• Not recommended without dietitian oversight, particularly in patients with nutritional deficiencies, eating disorder history, or pregnancy

Practical Considerations

Summary

• Cuffe et al. (2025). Lancet Gastroenterol Hepatol. PMID: 40258374
• Nybacka et al./CARIBS trial (2024). Lancet Gastroenterol Hepatol. PMID: 38643782
• ACG Low-FODMAP Diet resource
• Monash University FODMAP

What's inside (4 pages, A4, print-ready):

• Dark navy header banner with document title
• "What are FODMAPs?" explanation box (light blue)
• Full 5-category FODMAP table (Fructans, GOS, Lactose, Fructose, Polyols) with key food sources
• Three-phase protocol in colour-coded numbered boxes (green = Phase 1, blue = Phase 2, orange = Phase 3)
• Amber caution box on serving sizes + Monash App reference

• Side-by-side two-column layout:
  • Left (green): LOW-FODMAP safe foods across 9 categories
  • Right (red): HIGH-FODMAP foods to avoid in Phase 1
• Covers grains, vegetables, fruits, dairy, proteins, nuts/seeds, beverages, sweeteners, condiments

• 8 practical swap tips in a 2-column grid (garlic-infused oil, sourdough, lactose-free swaps, label reading, eating out etc.)
• Sample low-FODMAP day - 6 meals with practical notes
• Evidence summary box (CARIBS trial 2024 + Lancet network meta-analysis 2025)
• Red cautions/contraindications section